Registration Dossier

Ecotoxicological information

Endpoint summary

Administrative data

Description of key information

Additional information

Justification for grouping of substances and read-across

The Glycerides category covers aliphatic (fatty) acid esters of glycerol. The category contains both well-defined and UVCB substances with aliphatic acid carbon chain lengths of C2 (acetate) and C7-C22, which are mostly linear saturated and even numbered. Some of the substances in the category contain unsaturated fatty acids (e.g. oleic acid in 2,3-dihydroxypropyl oleate, CAS 111-03-5 or general fatty acids C16-22 (even) unsaturated in Glycerides, C14-18 and C16-22-unsatd., mono- and di-, CAS 91744-43-7). Some category members contain branched fatty acids. Branching is mostly methyl groups (e.g. isooctadecanoic acid, monoester with glycerol, CAS 66085-00-5 or 1,2,3-propanetriyl triisooctadecanoate, CAS 26942-95-0). In one category member the branching cannot be located precisely (Glycerides, C16-18 and C18-unsatd., branched and linear mono-, di- and tri, ELINCS 460-300-6). Hydroxylated fatty acids are present in three substances (Castor oil, CAS 8001-79-4; castor oil hydrogenated, CAS 8001-78-3 and 2,3-dihydroxypropyl 12-hydroxyoctadecanoate, CAS 6284-43-1). Hydroxylation occurs on C12 of stearic acid in all these substances. Acetylated chains are present in the last part of the category, comprising fatty acids from C8 to C18 (even) and also C18 unsaturated, additionally a C18 acetylated fatty acid is present with the acetic acid located in C12 position (e.g. Glycerides, castor oil mono-, hydrogenated acetates / 12-acetoxy-octadecanoic acid, 2,3-diacetoxy, CAS 736150-63-3). All glycerides build mono-, di- and tri-esters in variable proportions.

Fatty acid esters are generally produced by chemical reaction of an alcohol (e.g. glycerol) with an organic acid (e.g. acetic, stearic or oleic acid) in the presence of an acid catalyst (Radzi et al., 2005). The esterification reaction is started by the transfer of a proton from the acid catalyst to the acid to form an alkyloxonium ion. The carboxylic acid is protonated on its carbonyl oxygen followed by a nucleophilic addition of a molecule of the alcohol to the carbonyl carbon of the acid. An intermediate product is formed. This intermediate product loses a water molecule and proton to give an ester (Liu et al., 2006; Lilja et al., 2005; Gubicza et al., 2000; Zhao, 2000). Mono-, di- and tri-esters are the final products of esterification with glycerol.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be considered as a category provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substances listed below are allocated to the category of Glycerides.

The Glycerides category includes:

 

CAS

EC name

Molecular weight (range in case of UVCBs)

Fatty acids chain length

Degree of esterification

Molecular formula

26402-26-6 (b)

Octanoic acid, monoester with glycerol

218.29

C8

Mono

C11H22O4

142-18-7 (a)

2,3-dihydroxypropyl laurate

274.40

C12

Mono

C15H30O4

25496-72-4

Oleic acid, monoester with glycerol

356.54

C18:1

Mono

C21H40O4

111-03-5

2,3-dihydroxypropyl oleate

356.54

C18:1

Mono

C21H40O4

66085-00-5

Isooctadecanoic acid, monoester with glycerol

358.55

C18iso

Mono

C21H42O4

6284-43-1

2,3-dihydroxypropyl 12-hydroxyoctadecanoate

374.56

C18OH

Mono

C21H42O5

620-67-7

Propane-1,2,3-triyl trisheptanoate

428.60

C7

Tri

C24H44O6

538-23-8

Glycerol trioctanoate

470.68

C8

Tri

C27H50O6

538-24-9

Glycerol trilaurate

639.00

C12

Tri

C39H74O6

122-32-7

1,2,3-propanetriyl trioleate

885.43

C18:1

Tri

C57H104O6

555-43-1

Glycerol tristearate

891.48

C18

Tri

C57H110O6

26942-95-0

1,2,3-propanetriyl triisooctadecanoate

891.48

C18iso

Tri

C57H110O6

91052-47-0

Glycerides, C16-18 mono-

330.51 - 358.56

C16, C18

Mono

C19H38O4; C21H42O4

91744-09-1

Glycerides, C16-18 and C18-unsatd. mono-

330.51 - 358.56

C16, C18; C18uns.

Mono

C19H38O4; C21H42O4; C21H40O4

85536-07-8

Glycerides, C8-10 mono- and di-

218.29 - 400.60

C8, C10

Mono and di

C11H22O4; C13H26O4; C19H36O5; C23H44O5

91052-49-2

Glycerides, C12-18 mono- and di-

274.40 - 625.04

C12, C14, C16, C18

Mono and di

C15H30O4; C21H42O4; C27H52O5; C39H76O5

67701-33-1

Glycerides, C14-18 mono- and di-

302.45 - 625.02

C14, C16, C18

Mono and di

C17H34O4; C21H42O4; C31H60O5; C39H76O5

67784-87-6

Glycerides, palm-oil mono- and di-, hydrogenated

302.45 - 625.02

C14, C16, C18

Mono and di

C17H34O4; C21H42O4; C31H60O5; C39H76O5

91845-19-1

Glycerides, C16-18 and C18-hydroxy mono- and di-

330.51 - 657.02

C16, C18 C18OH

Mono and di

C19H38O4; C21H42O4; C35H68O5; C39H76O5; C21H42O5; C39H76O7

97358-80-0

Isooctadecanoic acid, mono- and diesters with glycerol

358.57 - 625.02

C18iso

Mono and di

C21H42O4; C39H76O5

91744-13-7

Glycerides, C14-18 and C16-22-unsatd. mono- and di-

302.45 - 733.20

C14, C16, C18, C16, C18 and C22uns.

Mono and di

C17H34O4; C21H42O4; C19H36O4; C25H48O4; C31H60O5; C39H76O5; C35H64O5; C47H88O5

31566-31-1

stearic acid, monoester with glycerol

330.51 - 325.03

C16, C18

Mono and di

C19H38O4; C21H42O4; C35H68O5, C39H76O5

85251-77-0

Glycerides, C16-18 mono- and di-

330.51 - 625.03

C16, C18

Mono and di

C19H38O4; C21H42O4; C35H68O5; C39H76O5

91744-32-0

Glycerides, C8-10 mono-, di- and tri-

218.29 - 554.84

C8, C10

Mono, di and tri

C11H22O4; C13H26O4; C19H36O5; C23H44O5; C27H50O6; C33H62O6

91052-28-7

Glycerides, C14-18 and C16-18-unsatd. mono-, di- and tri-

302.46 - 885.46

C14, C16, C18, C16:1, C18:1, C18:2, C18:3

Mono, di and tri

C17H34O4; C21H42O4; C19H36O4; C21H40O4; C31H60O5; C39H76O5; C35H64O5; C39H72O5; C45H86O6; C57H110O6; C51H92O6; C57H104O6

91052-54-9

Glycerides, C16-18 mono-, di- and tri-

330.50 - 891.48

C16, C18

Mono, di and tri

C19H38O4; C21H42O4; C35H68O5; C39H76O5; C51H98O6; C57H110O6

91744-20-6

Glycerides, C16-18 and C18-unsatd. mono-, di and tri-

330.51 - 891.50

C16, C18, C18uns.

Mono, di and tri

C19H38O4; C35H68O5; C51H98O6; C21H40O4; C39H72O5; C57H104O6

no CAS

ELINCS 460-300-6: Glycerides, C16-C18 and C18-unsaturated, branched and linear mono-, di- and tri-

330.51 - 891.50

C16, C18, C18uns., branched and linear

Mono, di and tri

C19H38O4; C35H68O5; C51H98O6; C21H40O4; C39H72O5; C57H104O6

97722-02-6

Glycerides, tall-oil mono-, di-, and tri-

356.54 - 885.43

C16, C18, C20, C18uns.

Mono, di and tri

C21H40O4; C39H72O5; C57H104O6

77538-19-3

Docosanoic acid, ester with 1,2,3-propanetriol

414.66 - 1059.80

C22

Mono, di and tri

C25H50O4; C47H92O5; C69H134O6

91744-28-4

Glycerides, C12-18 di- and tri-

456.70 - 891.50

C12, C14, C16, C18

Di and tri

C27H52O5; C39H76O5; C39H74O6; C57H110O6

68606-18-8

Glycerides, mixed coco, decanoyl and octanoyl

470.69 - 807.32

C8, C10, C12, C14, C16

Di and tri

C27H50O6; C33H62O6; C39H74O6; C45H86O6; C51H98O6

65381-09-1

Decanoic acid, ester with 1,2,3-propanetriol octanoate

470.69 - 554.85

C8, C10

Tri

C27H50O6; C33H62O6

73398-61-5

Glycerides, mixed decanoyl and octanoyl

470.69 - 554.85

C8, C10

Tri

C27H50O6; C33H62O6

85536-06-7

Glycerides, C8-18

470.68 - 891.48

C8, C10, C12, C14, C16, C18

Tri

C27H50O6; C57H110O6

67701-26-2

Glycerides, C12-18

639.01 - 891.48

C12, C14, C16, C18

Tri

C39H74O6; C57H110O6

67701-30-8

Glycerides, C16-18 and C18-unsatd.

807.32 - 891.48

C16, C18; C18uns.

Tri

C21H40O4; C39H72O5; C57H104O6

8001-79-4

Castor oil

933.43

C18:1(OH)

Tri

C57H104O9

8001-78-3

Castor oil, hydrogenated

939.48

C18OH

Tri

C57H110O9

97593-30-1

Glycerides, C8-21 and C8-21-unsatd. mono- and di-, acetates

330.42 - 442.63

C2; C10

Tri (FA mono, diacetate)

C17H30O6; C25H46O6

97593-30-1

Glycerides, C8-21 and C8-21-unsatd. mono- and di-, acetates

358.47 - 498.74

C2; C12

Tri (FA mono, diacetate)

C19H34O6; C29H54O6

93572-32-8

Glycerides, palm-oil mono-, hydrogenated, acetates

372.54 - 400.59

C2; C16

Tri (FA mono, diacetate)

C21H40O5; C23H44O5

91052-13-0

Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates

302.36 - 442.63

C2; C8, C10, C12, C14, C16, C18, C18uns.

Mono, di and tri

C15H26O6; C19H34O6; C21H38O6; C25H46O6

736150-63-3

Glycerides, castor-oil-mono, hydrogenated, acetates (main component: 12-acetoxy-octadecanoic acid (2,3-diacetoxy)propyl ester [CAS 330198-91-9])

500.67

C2; C18Ac

Tri (FA mono, diacetate)

C27H48O8

no CAS (c, d)

Short-, medium- and long-chain triglycerides (SCT, MCT, LCT)

-

C2-C18 (even numbered), C18uns.

Tri

-

no CAS (c, d)

mixture of mono-, di-, and triglycerides of lauric acid

274.40 - 639.00

C12

Mono, di and tri

C15H30O4; C27H52O5; C39H74O6

no CAS (c, d)

Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

833.36 - 859.39

C16, C18, C18uns.

Tri

C53H100O6; C55H102O6

56-81-5 (c)

Glycerol

92.09

--

--

C3H8O3

111-14-8 (c)

Heptanoic acid

130.18

C7

--

C7H14O2

112-85-6 (c)

Docosanoic acid

340.58

C22

--

C22H44O2

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for these substances a full set of experimental results and/or read-across is given.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

(c) Surrogate substances are either chemicals forming part of a related category of structurally similar fatty acid esters or precursors/breakdown products of category members (i.e. alcohol and fatty acid moieties). Available data on these substances are used for assessment of (eco )toxicological properties by read-across on the same basis of structural similarity and/or mechanistic reasoning as described below for the present category.

(d) Assessment of toxicological properties is conducted also taking into account available data on mixtures of synthetic and/or naturally occurring glycerides (e.g. vegetable oils), which cannot be identified by a (single) CAS/EC number. The test materials short-, medium- and long-chain triglycerides (SCT, MCT, LCT) and their combinations (e.g. MLCT, SALATRIM – a SLCT) comprise triesters of glycerol with fatty acid chain lengths of C2 and C4 (short-chain), C8 and C10 (medium-chain) and C18 saturated/unsaturated (long-chain). The substance “mixture of mono-, di-, and triglycerides of lauric acid” comprises mono-, di and triesters of glycerol with dodecanoic acid (C12). The substance “Modified triglyceride” contains main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol, comprising triesters of glycerol with hexadecanoic (C16) and (9Z)-Octadec-9-enoic acid (C18:1). Available data on identity and composition of the individual test material for a given study is provided in the technical dossier.

 

Grouping of substances into this category is based on:

(1) common functional groups:all members of the Glycerides category are esters of a tri-functional alcohol (glycerol) with one or more carboxylic (fatty) acid(s) chain(s). The alcohol moiety (glycerol) is common to all category members. The fatty acid moiety comprises carbon chain lengths of C2 (acetate) and from C7-C22 (uneven/even-numbered) and includes mainly linear saturated alkyl chains, but also unsaturated, branched, hydroxylated and acetylated chains bound to the alcohol, resulting in mono-, di-, and tri-esters; and

(2) common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals:all members of the Glycerides category result from esterification of glycerol with the respective fatty acid(s). Esterification is, in principle, a reversible reaction (hydrolysis). Thus, the glycerol and fatty acid moieties are simultaneously precursors and breakdown products of Glycerides. For the purpose of grouping of substances, enzymatic hydrolysis in the gastrointestinal tract and/or liver is identified as the biological process, by which the breakdown of Glycerides result in structurally similar chemicals. Furthermore, hydrolysis represents the first chemical step in the absorption, distribution, metabolism and excretion pathways anticipated to be similarly followed by all Glycerides (CIR, 1984, 2004, 2007; Elder, 1990, 1982, 1986; FDA, 1975; Johnson, 2001; Lehninger, 1998; NTP, 1994; Stryer, 1996; WHO, 1967, 1974, 1975, 1979, 2001). Hydrolysis is catalysed by a class of enzymes known as lipases, a subgroup of carboxylesterases. In general, Glycerides are enzymatically hydrolysed in the small intestine to glycerol and corresponding carboxylic acid(s), and in the case of di- and triglycerides also to monoglycerides (with the ester bond at the sn-2 position). Following hydrolysis, glycerol is readily absorbed through the gastrointestinal tract and can be re-esterified to form endogenous glycerides or be metabolised to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, which can be incorporated in the standard metabolic pathways of glycolysis and gluconeogenesis. Being a polar molecule, glycerol can also be readily excreted in the urine. Fatty acids are likewise readily absorbed by the intestinal mucosa and distribute systemically. Fatty acids are a source of energy. They are either re-esterified into triacylglycerols and stored in adipose tissue, or enzymatically degraded for energy primarily via β-oxidation. Alternative oxidation pathways (alpha- and omega-oxidation) are available and are relevant for degradation of branched fatty acids. Unsaturated fatty acids require additional isomerization prior to enter the β-oxidation cycle. Acetate, resulting from hydrolysis of acetylated Glycerides, is readily absorbed and feeds naturally into physiological pathways of the body and can be utilized in oxidative metabolism or in anabolic syntheses; and

(3) constant pattern in the changing of the potency of the properties across the category:the available data show similarities and trends within the category in regard to physicochemical, environmental fate, ecotoxicological and toxicological properties. For those individual endpoints showing a trend, the pattern in the changing of potency is clearly and expectedly related to the length of the fatty acid chains and the degree of substitution of glycerol (mono-, di- or triester).

a) Physicochemical properties:

The physico-chemical properties of the category members are similar or follow a regular pattern over the category. The patterns observed depend on the fatty acid chain length and the degree of esterification (mono-, di- or triester).

The molecular weight of the category members (glycerol esters) ranges from 218.29 to 1059.80 g/mol. The physical state is related to the chain length of the fatty acid moiety, the degree of saturation and the number of ester bonds. Thus, monoesters of short- and long-chain fatty acids (C8-C12) as well as unsaturated (C18:1) fatty acids and C18OH are solids, whereas monoesters of branched fatty acids (C18iso) are liquids. Triesters of shorter-chain fatty acids (C8-12) as well as unsaturated (C18:1) and branched longer-chain acids (C18iso) are liquids. The physical state of mixtures of mono-, di- and tri-esters depends on the amount of different esters. Mono-, di- and tristers of shorter-chain fatty acids are liquid (C8-12), mono-, di- and tristers of longer-chain fatty acids are solids (C14-18, C18OH and also C18iso). The turning point of this property seems to be fatty acids C12. In addition, mono- and diesters with a certain amount of unsaturated acids are liquids. Following the described pattern the UVCB triesters of shorter-chain fatty acids (C8-14) and unsaturated fatty acids (C18:1 and C18:1OH) are liquids. For the glycerides with acetic acid (mainly monoester of fatty acids and diester of acetic acid) the turning point seems to be the fatty acid chain length C14/C16. Below this point the substances are liquid, above this point category members are solid.

Also the boiling points are following a pattern: Increasing molecular weight results in increasing boiling temperatures. For a molecular weight of below 300 g/mol the boiling point is around 170 °C (C12 monoester), between a molecular weight of 350 to 480 g/mol the boiling point is between 230-300 °C. Above 300 g/moles the decomposition of the substances is probable. Also the acetate esters have boiling points >300 °C. According to Blake et al. (J. Chem. Eng. Data, 1961, 6, 87-98), esters of long chain acids with β‑hydrogen atoms in the alcohol moiety (i.e. alcohols with C3, e.g. propanol) decompose in the range between 262 and 283 °C. Since for longer chains the boiling temperature is higher, esters of fatty acids esterified with alcohols ≥ C3 and having a molecular weight exceeding 300 amu have a boiling point >300 °C and decompose before boiling.

All category members are non-volatile with a vapour pressure <0.01 Pa at temperature of 20 °C, mainly based on (Q)SAR calculation.

The n-octanol/water partition coefficient increases with increasing chain length and increasing degree of esterification (e.g. C8 monoester: 1.71; C7 triester: 8.86; C22 triester >15). A positive correlation with the overall number of CH2 units is observed.

The water solubility decreases accordingly with increasing chain length or increasing overall number of CH2 units (20-60 mg/L for C8 monoester to <0.05 mg/L for C7 triester; <4 mg/L for C18:1 monoester to <0.05 mg/L for C18iso monoester). The cut-off value for water solubility below 1 mg/L seems to be the C16 to C18 monoester. Fo higher degree of esterification (di and triesters) other limits are applicable: a C12 diester at least has a water solubility of below 1 mg/L, the C7 triester has a solubility well below 1 mg/L. The water solubility depends on the method used for testing and for analysis of test item. Testing by GC-MS is more selective than testing by TOC/DOC method, GC-MS results are therefore lower than results obtained by TOC. Nevertheless a correlation between increasing molecular weight and decreasing water solubility can be found.

b) Environmental fate and ecotoxicological properties:

The members of the Glycerides category are readily biodegradable and show low bioaccumulation potential in biota. Hydrolysis is not a relevant degradation pathway for these substances, due to their ready biodegradability and estimated half-lives in water > 250 days at pH 7 and 25 days at pH 8 (HYDROWIN v2.00). The majority of the Glycerides category members have log Koc values > 3, indicating potential for adsorption to solid organic particles. Therefore, the main compartments for environmental distribution of these substances are expected to be soil and sediment, with the exception of 2,3-dihydroxypropyl laurate (CAS 142-18-7), for which a log Koc < 3 is reported. Therefore, this substance will be most likely available in the water phase. Nevertheless, all substances are readily biodegradable, indicating that persistency in the environment is not expected. The volatilization potential of the Glycerides category members is negligible, based on vapour pressure values ranging from < 0.0001 Pa to < 5 Pa at 20°C. Nevertheless, if released into the atmosphere, these substances are expected to be rapidly photodegraded in view of their estimated half-lives in air, ranging from 1.5 to 20.7 hours (AOPWIN 1.92 program). Based on the above information, accumulation in air, subsequent transportation through the atmosphere and deposition into other environmental compartments is not anticipated. Regarding aquatic toxicity, acute and chronic values obtained in tests conducted on fish, invertebrates, algae and microorganisms showed no adverse effects in the range of the water solubility of the substances (or the highest attainable solubility in aqueous medium), with the exception of Glycerides, palm-oil mono-, hydrogenated, acetates (CAS 93572-32-8). Even though it cannot be excluded that for this substance the observed effects are due to physical interference with undissolved test material (particulate material observed in test solutions), the NOEC value of the algae test is < 1 mg/L (0.565 mg/L) and within the water solubility range of the substance (1.3-7.4 mg/L). Therefore, a conservative approach is applied and the substance classified as environmental hazard Chronic category 3, according to Regulation (EC) No. 1272/2008. Based on the available data, no toxicity to aquatic microorganisms, sediment and terrestrial organisms is to be expected for the substances of the Glycerides category.

c) Toxicological properties:

The available data shows that the category of Glycerides is characterised by a lack of change of the potency of toxicological properties. No human health hazard is identified. Thus, all available studies consistently show that Glycerides are not acutely toxic via the oral, dermal and inhalation routes. The available animal and human studies indicate that Glycerides are not skin or eye irritating and not skin sensitising. All available in vitro and in vivo genetic toxicity studies are negative for the induction gene mutations in bacteria and mammalian cells and of chromosome aberrations or micronuclei in mammalian cells. No adverse effects were observed up to, including and even well above the limit dose of 1000 mg/kg bw/day in the available short- and long-term toxicity studies via the oral route. Likewise, no reproductive toxicity effects were observed in any of the available studies.

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13).

The Aquatic toxicity parameters of the Glycerides category are presented in the table below.

CAS

Short term toxicity to fish

Long term toxicity to fish

Short term toxicity to aquatic invertebrates

Long term toxicity to aquatic invertebrates

Toxicity to aquatic algae

Toxicity to microorganisms

142-18-7 (a)

On-going study

Waiving

Waiving

On-going study

On-going study

On-going study

6284-43-1

RA: CAS 8001-78-3

Waiving based on CSA

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS         122-32-7

620-67-7

Experimental result:
LC50 (96 h) > 64 mg/L

Waiving based on CSA

 

Experimental result:
EC50 (48 h) >3.9 mg/L

On-going study

Experimental result:
EC50 (72 h) >1.8 mg/L

Experimental result:
NOEC ≥ 40.7 mg/L
(biodegradation test)

122-32-7

WoE:
Experimental result:
LC50(48 h) >1000 mg/L
+ RA: CAS 91052-28-7

Waiving based on CSA

RA: CAS 91052-28-7

RA: CAS 91052-28-7

Experimental result:
IC50 (72 h) >5 mg/L

Experimental result:
NOEC(18 h) ≥0.8 mg/L

555-43-1

RA: CAS 8001-78-3
RA: CAS 620-67-7

Waiving based on CSA

RA: CAS       620-67-7

RA: CAS 620-67-7

RA: CAS   620-67-7

RA: CAS 8001-78-3

85536-07-8

Experimental result:
LL50 (96 h)= 75 mg/L (nominal)

Waiving

Experimental result:
EL50(48 h)= 218.2 mg/L (nominal)

EL50(48 h)= 102.6 mg/L (measured)

 

Expert statement

Experimental result:
EL50 (72 h)= 49 mg/L (nominal)

NOELR(72 h)= 20.7 mg/L (nominal)

NOELR(72 h)= 1.19 mg/L (measured)

Experimental result:
NOEC ≥ 46.9 mg/L
(toxicity control biodegradation test)

91052-49-2

Experimental result:
LL50 (96 h)

> 20 mg/L (nominal)

LL50 (96h)  

> 2.7 mg/L (measured)

Waiving

Experimental result:
EL50(48 h)= 36.2 mg/L (nominal)

EL50(48 h)= 5.6 mg/L (measured)

Expert statement

Experimental result:
EL50 (72 h)= 13 mg/L

NOELR(72 h)= 4.1 mg/L

RA: CAS       91744-28-4

67701-33-1

 

Experimental result:
LC50(96 h) >10000 mg/L

Waiving based on CSA

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS          122-32-7

67784-87-6

RA: CAS 67701-33-1

Waiving based on CSA

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS           122-32-7

97358-80-0

RA: CAS 8001-78-3

Waiving based on CSA

 

Experimental result:
EL50 (48 h) >100 mg/L

RA: CAS 91052-28-7

RA: CAS 91052-28-7

 

RA: CAS         122-32-7

91052-28-7

WoE:
Experimental result:
LC50(48 h) >10000 mg/L
+ RA: CAS       122-32-7

Waiving based on CSA

Experimental result:
EL50 (48 h) >100 mg/L

Experimental result:
NOELR(21d) >10 mg/L

Experimental result:

ErL50 (72 h) >320 mg/L
NOELR (72 h) = 32 mg/L

RA: CAS         122-32-7

91052-54-9

RA: CAS  67701-33-1

Waiving based on CSA

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS          122-32-7

97722-02-6

--

--

Experimental result:
EL50(48 h) >100 mg/L

--

--

--

77538-19-3

Experimental result:
LC50(96 h) >10000 mg/L

Waiving based on CSA

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS        122-32-7

91744-28-4

RA: CAS  91052-49-2

Waiving

RA: CAS 91052-49-2

Expert statement

RA: CAS 91052-49-2

Experimental result:
NOEC ≥ 41.1 mg/L
(toxicity control biodegradation test)

68606-18-8

RA: CAS      620-67-7

RA: CAS      122-32-7

RA: CAS  91052-28-7

Waiving based on CSA

RA: CAS      620-67-7

RA: CAS 91052-28-7

 

RA: CAS 620-67-7

RA: CAS 91052-28-7

 

RA: CAS    620-67-7

RA: CAS   122-32-7

RA: CAS 91052-28-7

RA: CAS            122-32-7

65381-09-1

--

--

Experimental result:
EC50(48 h)     > 0.01 mg/L

Experimental result:
NOEC(21 d) ≥0.01 mg/L

Experimental result:
EC50 (72 h) >0.01 mg/L

--

73398-61-5

Experimental result:
LC50(96 h) >53 mg/L

--

--

--

Experimental result:
EC50 (72 h) >0.449 mg/L

--

85536-06-7

RA: CAS   85536-07-8

RA: CAS   91052-49-2

RA: CAS  8001-78-3

Waiving

RA: CAS 85536-07-8

RA: CAS 91052-49-2

RA: CAS 91052-28-7

RA: CAS 91052-28-7

RA: CAS 85536-07-8

RA: CAS 91052-49-2

RA: CAS 91052-28-7

RA: CAS    85536-07-8

RA: CAS    122-32-7

67701-30-8

Experimental result:
LC50(96 h) >10000 mg/L

--

Experimental result:
EC50(48 h)     > 0.01 mg/L

--

Experimental result:
EC50 (72 h) >0.01 mg/L

--

8001-78-3 (b)

Experimental result:
LC50(96 h) >10000 mg/L

--

--

--

--

Experimental result:
NOEC ≥ 100 mg/L
(biodegradation test)

97593-30-1 (C10)

RA: CAS  97593-30-1 (C12)

Waiving based on CSA

RA: CAS 97593-30-1 (C12)

RA: CAS 97593-30-1 (C12)

RA: CAS 97593-30-1 (C12)

RA: CAS    97593-30-1 (C12)

97593-30-1 (C12)

Experimental result:
LC50 (96 h) >100 mg/L

Waiving based on CSA

Experimental result:
EC50(48 h) >0.11 mg/L

Experimental result:
NOEC (21 d) >10 mg/L

Experimental result:
EC50 (72 h) >0.264 mg/L

NOEC ≥ 100 mg/L
(toxicity control biodegradation test)

93572-32-8

Experimental result:
LC50(96 h) >77.9 mg/L

Exposure based waiving

Experimental result:
EC50 (48 h) =64.4 mg/L

Exposure based waiving

Experimental result:
EC50 (72 h) >72.6 mg/L
NOEC(72 h) = 0.57 mg/L

NOEC ≥ 100 mg/L
(toxicity control biodegradation test)

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for these substances a full set of experimental results and/or read-across is given.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The Glycerides category members are structurally similar and read-across (according to Regulation (EC) No. 1907/2006, Annex XI, 1.5) was performed to the structurally most similar category members when necessary to fulfil the information requirements present in Annexes VII-IX of the REACh Regulation. Generally, no effects occurred up to the limit of the water solubility of the substances, with a few exceptions, which are discussed below. The Glycerides category members are considered as “difficult to test” substances, according to the criteria of the OECD 23 Guideline on Aquatic toxicity testing of difficult substances and mixtures. All substances included in the category fall under one or more properties considered as challenging when conducting aquatic toxicity tests. The majority of the substances are poorly soluble in water and highly adsorbing. Furthermore, most of them are complex mixtures of several components, which might have a different solubility in the water phase. The aquatic toxicity tests conducted with the Glycerides category members take into consideration these characteristics and modifications or additions to standard testing procedures were done, if appropriate.

There are 28 Glycerides (registered or subject of registration) within the category: three monoconstituent substances, 2 multiconstituent substances (currently under the same case number) and 23 UVCB substances.

There are three monoconstituent substances within the category, propane-1,2,3-triyl trisheptanoate (CAS 620-67-7, triglyceride, C7 fatty acid), glycerol tristearate (CAS 555-43-1, triglyceride, C18 fatty acid) and 2,3-dihydroxypropyl laurate (CAS 142-18-7, monoglyceride, C12 fatty acid). The acute tests conducted on fish, aquatic invertebrates and algae with CAS 620-67-7 showed no toxicity of the substance up to the limit of its water solubility (WS < 0.05 mg/L). Long-term toxicity was investigated in a test conducted according to OECD 211 under semi-static conditions, using Daphnia magna as test organisms. A loading rate of 100 mg/L (nominal) was applied in this limit test. As the test concentration was not low enough to show that the reproductive output at that concentration is not significantly lower than that in the control, OECD 211 (page 6, paragraph 35) states ‘If this is not the case, the test should be repeated with a reduced lowest concentration’. Therefore, the study is disregarded and a new test will be performed with a reduced test concentration. The IUCLID dossier will be updated as soon as possible and the chemical safety assessment re-evaluated based on the results of this new test. Read-across data from castor oil, hydrogenated (CAS 8001-78-3) and propane-1,2,3-triyl trisheptanoate (CAS 620-67-7, triglyceride, C7 fatty acid) were used to evaluate the toxicity of glycerol tristearate (CAS 555-43-1) to aquatic organisms. All three substances are esters formed from the combination between fatty acids and glycerol. Propane-1,2,3-triyl trisheptanoate and glycerol tristearate are triglycerides (the three hydroxyl functional groups of the glycerol molecule are esterified with fatty acids), differing only in the length of the C-chain of their fatty acid components (C7 and C18 respectively). Castor oil hydrogenated is predominantly a C18 hydroxylated triglyceride, therefore sharing the same C-chain length as glycerol tristearate. The behaviour of these three substances in the water phase is expected to be very similar based on low water solubility values (< 1 mg/L) and high log Pow (>8). Nevertheless, the bioavailability of glycerol tristearate and castor oil hydrogenated to aquatic organisms is expected to be lower than that of propane-1,2,3-triyl trisheptanoate due to their high molecular weight (> 700 g/Mol) which can hinder the crossing of biological membranes (Guidance on information requirements and chemical safety assessment, Chapter R.11 (ECHA, 2012). Based on this information, reading-across from castor oil hydrogenated and propane-1,2,3-triyl trisheptanoate to glycerol tristearate (CAS 555-43-1) is justified and, in the case of propane-1,2,3-triyl trisheptanoate, can be considered as a worst-case approach. The acute fish test conducted with CAS 8001-78-3 showed no toxicity up to a nominal concentration of 10,000 mg/L. This result in combination with the acute values for CAS 620-67-7, indicate that glycerol tristearate (CAS 555-43-1) is not expected to exhibit toxicity to aquatic organisms up to the limit of its water solubility (WS < 1 mg/L). Regarding 2,3-dihydroxypropyl laurate (CAS 142-18-7, monoglyceride, C12 fatty acid), acute tests on fish, algae and aquatic microorganisms and a chronic Daphnia sp. test are currently on-going. This IUCLID dossier will be updated as soon as possible and the chemical safety assessment re-evaluated based on the results of the new tests.

Glycerides, C8-10 mono- and di (CAS 85536-07-8), Glycerides, C12-18 mono- and di- (CAS 91052-49-2), Glycerides, C12-18 (CAS 67701-26-2) and Glycerides, mixed decanoyl and octanoyl (CAS 73398-61-5) represent the short-to-medium fatty acid C-chain length spectrum of the UVCB substances. Glycerides, C12-18 (CAS 67701-26-2) and Glycerides, mixed decanoyl and octanoyl (CAS 73398-61-5) are poorly soluble substances (WS < 1 mg/L) due to their high degree of esterification (triester > 90%). Therefore, acute and chronic toxicity data from other triglycerides, decanoic acid, ester with 1,2,3-propanetriol octanoate (CAS 65381-09-1), Glycerides, C16-18 and C18 unsatd. (CAS 67701-30-8) and castor oil, hydrogenated (CAS 8001-78-3) were used as read-across. The acute tests conducted on fish, aquatic invertebrates and algae, and the chronic test conducted on aquatic invertebrates showed no toxicity of these substances up to the limit of the water solubility (or the highest attainable solubility in aqueous medium).

Glycerides, C8-10 mono- and di (CAS 85536-07-8), Glycerides, C12-18 mono- and di- (CAS 91052-49-2) are assumed to be relatively water soluble (WS 46 and 3.3 mg/L, respectively), however these results should be treated with caution due to the tendency of mono- and diesters to form microemulsions which may skew water solubility analyses by TOC. The acute tests conducted on fish, aquatic invertebrates and algae with CAS 85536-07-8 reported effects of the substance to these organisms at concentrations above the water solubility of the substance (46 mg/L). LL/EL50 values for fish, aquatic invertebrates and algae were 75, 218.2 and 49 mg/L. On the other hand, the NOEC for algae was 20.7 mg/L. In this test, the algae were reported to be encased by small dispersed particles in the suspension (confirmed by microscopical observation). Therefore, a physical interference of test substance particles with algae cells may also have contributed to the observed effect. The Guidance on information requirements and chemical safety assessment, Chapter R7.b, states that poorly water-soluble substances often have technical difficulties during aquatic testing, therefore one should treat results from tests above the limit of solubility with care and they “should not be interpreted as pelagic toxicity, but as confounded by physical effects” (ECHA, 2012).

Thus, this also may have been the case in the two experimental studies conducted with fish and aquatic invertebrates with Glycerides, C8-10 mono- and di (CAS 85536-07-8). However, since intrinsic toxicity cannot be excluded, to be on the safe side, the values are used for the assessment of aquatic toxicity. Nevertheless, due to the readily biodegradable nature of the substance, such high concentrations are no expected to be reached in natural waters. Therefore, in accordance with the 2nd ATP of Regulation (EC) No.1272/2008, the substances are not classified as dangerous for the environment. Comparable results were observed in the acute tests performed with the other short-to-medium fatty acid C-chain substance, Glycerides, C12-18 mono- and di- (CAS 91052-49-2) on fish, aquatic invertebrates and algae. In this case, no toxicity up to the limit of water solubility was observed in fish, leading to a LL50 > 20 mg/L (highest tested concentration). Nevertheless, effects were observed in the tests conducted on aquatic invertebrates and algae, with EL50 values of 36.2 mg/L and 13 mg/L, respectively, and a NOELR of 4.1 mg/L in the algae test. All the effect concentrations are above the water solubility of the substance (WS = 3.3 mg/L). Once again, physical effects cannot be excluded. Scientific evidence proves that aquatic toxicity testing of this type of Glycerides is technically very difficult. In an article by Prajapati et al. (2012), the phase behaviour of lipid/surfactant/water phases was investigated, where medium-chain (C8-10) mono-, di- and triglycerides represent the lipid. Phase boundaries between lipids (monoglycerides, diglycerides, triglycerides), surfactant (PEG-35 castor oil) and water were established by visual inspection after an equilibration period, and the results expressed in phase diagrams. Viscosity and particle size distribution were measured. The mixtures with monoglyceride displayed two predominant phases: microemulsion and emulsion phases, whereas di- and triglycerides showed additionally a gel phase. Mixtures of monoglycerides and diglycerides, and of monoglycerides and triglycerides seemed to promote an increase of the microemulsion phase (in the 4 phases equilibrium). Particle size in these mixtures was found to be much smaller than in the monoglyceride sample alone. Microemulsions are solutions with an average particle size < 0.2 µm. This particle size would not be intercepted by a standard filter used in an aquatic toxicity test (generally, pore size of 0.45 µm). Due to their small size, based on visual inspection, clear or translucent solutions might be observed even when these microemulsions are present. Considering this information and the results of the tests conducted on Glycerides, C8-10 mono- and di (CAS 85536-07-8) and Glycerides, C12-18 mono- and di- (CAS 91052-49-2), no toxicity up to the highest attainable solubility of these substances (before microemulsion formation) is expected. The results of the upcoming long-term Daphnia test currently on-going on the C12 monoconstituent substance (CAS 142-18-7) will show the chronic behavior of this substance and could potentially be used as read-across for the above mentioned substances. The data available for Glycerides, C12-18 mono- and di- (CAS 91052-49-2) are used as read-across for the structurally similar Glycerides, C12-18 di- and tri- (CAS 91744-28-4), as both substances differ mainly in their degree of esterification. Due to the higher degree of esterification of the target substance, the crossing of biological membranes might be hindered with respect to the source substance, and therefore, this read-across can be considered as a worst-case.

Sixteen out of the 23 UVCB substances represent the longest fatty acid C-chain lengths within UVCBs of the category. These substances are characterized by a poor solubility in water (WS range from < 0.05 mg/L to < 1 mg/L) and a similar structure. They contain mainly C16-18 fatty acids, and lower amounts of other C-chain lengths, and high contents of mono- and diglycerides (with the exception of 1,2,3-propanetriyl trioleate (CAS 122-32-7) and castor oil, hydrogenated (CAS 8001-78-3), triglycerides). The acute fish tests conducted on 1,2,3-propanetriyl trioleate (CAS 122-32-7), Glycerides,C14-18 and C16-18 unsatd, mono-, di- and tri- (CAS 91052-28-7), Glycerides, C14-18 mono- and di- (CAS 67701-33-1), castor oil, hydrogenated (8001-78-3), Glycerides, mixed octanoyl and decanoyl (CAS 73398-61-5) and docosanoic acid, ester with 1,2,3-propanetriol (CAS 77538-19-3) showed no toxicity of these substances up to the limit of their water solubility (LC50 values > 50 to > 10000 mg/L). Within this group, five reliable acute tests conducted on Daphnia sp. are available, for Glycerides,C14-18 and C16-18 unsatd, mono-, di- and tri- (CAS 91052-28-7), isooctadecanoic acid, mono- and diesters with glycerol (CAS 97358-80-0), decanoic acid, ester with 1,2,3-propanetriol octanoate (CAS 65381-09-1), Glycerides, C16-18 and C18 unsatd. (CAS 67701-30-8) and Glycerides, tall-oil, mono-, di- and tri- (CAS 97722-02-6). All tests reported no immobilization up to the limit of water solubility or the highest attainable concentration in test solution (E(C)L50 values > 0.01 mg/L to > 100 mg/L). Two reliable long-term toxicity tests conducted on aquatic invertebrates are available, for Glycerides, C14-18 and C16-18 unsatd, mono-, di- and tri- (CAS 91052-28-7) and decanoic acid, ester with 1,2,3-propanetriol octanoate (CAS 65381-09-1). The most recent reliable study is now used as read-across for the other long-chain UVCBs, due to their structural similarities. Furthermore, Glycerides, C14-18 and C16-18 unsatd, mono-, di- and tri- (CAS 91052-28-7) has a high content of C18 unsaturated fatty acids. In a publication by Wu et al. (2006), it was demonstrated that free C18 unsaturated fatty acids were consistently more toxic than C18 saturated fatty acids to aquatic organisms. Based on the above information, read-across from Glycerides, C14-18 and C16-18 unsatd, mono-, di- and tri- (CAS 91052-28-7) to other long-chain UVCB substances within the category is considered as a worst-case and it is justified. In both chronic studies, no adverse effects on survival, growth or reproduction of Daphnia magna were observed up to a nominal concentration of 10 mg/L (CAS 91052-28-7) and a measured concentration of 0.01 mg/L (highest attainable concentration for CAS 65381-09-1). Four algae studies are available, for 1,2,3-propanetriyl trioleate (CAS 122-32-7), Glycerides, C16-18 and C18 unsatd. (CAS 67701-30-8), Glycerides, mixed octanoyl and decanoyl (CAS 73398-61-5) and Glycerides, C14-18 and C16-18 unsatd., mono-, di- and tri- (CAS 91052-28-7). The first three studies reported no toxicity up to the limit of water solubility or the highest attainable concentration in test solution (E(C)L50 values > 0.01 mg/L to > 5 mg/L). The fourth study, conducted with CAS 91052-28-7, resulted in effects at concentrations above 32 mg/L, leading to an ErL50 > 320 mg/L and a NOEC of 32 mg/L, both well above the water solubility of the substance (WS < 0.05 mg/L). The stock solutions were reported to be clear and colourless but once again, due to the fact that the effects are observed above the water solubility value for this substance, physical effects cannot be excluded. This study was considered as most suitable for read-across for the long-chain UVCB substances within the category for which no data are available.

Two of the 23 UVCB substances within the category, cover a broad range of fatty acid C-chain lengths (C8-18). No experimental data evaluating the toxicity to aquatic organisms of Glycerides, mixed coco, decanoyl and octanoyl (CAS 68606-18-8) and Glycerides, C8-18 (CAS 85536-06-7) are not available. Since they both cover a wide range of fatty acid C-chain lengths (C8-18 and additionally C18 unsaturated for CAS 68606-18-8), for which results are available, read-across from the most structurally similar substances within the category was performed. Glycerides, mixed coco, decanoyl and octanoyl (CAS 68606-18-8) is poorly soluble in water (WS < 0.05 mg/L) and therefore, read-across data from propane-1,2,3-triyl trisheptanoate (CAS 620-67-7, monoconstituent, C7 fatty acid) and Glycerides,C14-18 and C16-18 unsatd, mono-, di- and tri- (CAS 91052-28-7) is performed. The two read-across substances cover the whole fatty acid C-chain range present in Glycerides, mixed coco, decanoyl and octanoyl and as such they are considered to give a good indication of the expected toxicity of the substance to aquatic organisms. On the other hand, Glycerides, C8-18 (CAS 85536-06-7) has a water solubility of 2 mg/L and therefore, Glycerides, C8-10 mono- and di (CAS 85536-07-8) and Glycerides, C12-18 mono- and di- (CAS 91052-49-2) are used as read-across representing the short-to-medium fatty acid C-chain length spectrum of this substance. Furthermore, read-across from Glycerides,C14-18 and C16-18 unsatd, mono-, di- and tri- (CAS 91052-28-7) is performed to cover the potential toxicity of long-chain fatty acids.

Two multiconstituent substances and one UVCB substance containing acetylated fatty acids are also present in the category. Glycerides, C8-21 and C8-21 unsatd., mono- and di- acetates (CAS 97593-30-1, both C10 and C12 registrations) showed no toxicity up to nominal concentrations of 100 mg/L in acute tests conducted on fish, Daphnia and algae, and up to 10 mg/L in a chronic test performed with Daphnia magna. On the other hand, effects were observed on the tests conducted with Glycerides, palm-oil mono-, hydrogenated, acetates (CAS 93572-32-8). The acute test conducted on fish species showed no effects up to highest tested concentration of 77.9 mg/L. Significant effects were reported in the acute tests conducted with aquatic invertebrates and algae, with an EC50 value of 64.4 mg/L for Daphnia magna and a NOEC of 0.565 mg/L for Pseudokirchneriella subcapitata. The calculated effect concentration from the Daphnia test (64.4 mg/L) is well above the water solubility of the test substance (WS = 1.3-7.4 mg/L). In this test, precipitated test substance was observed in all test solutions and particulate material was found attached to the test organisms. Therefore, it cannot be concluded if the observed immobilization was due to the intrinsic toxicity of the substance, or due to physical interference with undissolved test material. Precipitated test substance was also present in the test solutions from the algae test, and once again physical effects cannot be ruled out. Nevertheless, due to the fact that toxicity in the algae test was observed within the range of water solubility of the substance, a conservative approach was taken and the reported NOEC value was determined to meet the criteria for classification according to the 2nd ATP of Regulation (EC) No. 1272/2008 (CLP, Chronic Category 3). This NOEC is considered as key value for the chemical safety assessment of this substance.

In summary, the Glyceride category members show no acute toxicity to fish, aquatic invertebrates and algae or chronic effects in aquatic invertebrates up to the limit of water solubility (or the highest attainable solubility until the formation of microemulsions in the case of medium-chain glycerides), with the exception of Glycerides, palm-oil mono-, hydrogenated, acetates (CAS 93572-32-8). Based on the short term values, fish cannot be identified as the most sensitive organism. According to the Guidance on information requirements and chemical safety assessment, Chapter R7.b (ECHA, 2012), long-term toxicity testing on fish should only be conducted if it represents the most sensitive taxonomic group. The Guidance states that if invertebrates are likely to be more sensitive than fish or the relative sensitivity of invertebrates cannot be predicted, long-term testing on Daphnia sp. should be preferred instead of fish. Considering this information, long-term toxicity testing on fish species is not deemed necessary for the Glycerides category members.

Toxicity to aquatic microorganisms is not anticipated for the Glyceride category members. All substances are readily biodegradable. According to the Guidance on information requirements and chemical safety assessment, Chapter R7.b (ECHA, 2012), the assumption that a certain substance is not inhibitory of microorganisms activity is implicit in ready biodegradability tests. If a compound degrades well in such a test, or does not inhibit the biodegradation of a positive control at a certain concentration, this concentration can be used as NOEC value. The biodegradation tests performed with Glycerides, C8-10 mono- and di (CAS 85536-07-8), Glycerides, C12-18 di- and tri- (CAS 91744-28-4), Glycerides, C8-21 and C8-21 unsatd., mono- and di- acetates and (CAS 97593-30-1) and Glycerides, palm-oil mono-, hydrogenated, acetates (CAS 93572-32-8) showed that more than 50% biodegradation in the toxicity controls occurred within 14 days, clearly indicating lack of toxicity to activated sludge microorganisms. The test available for 1,2,3-propanetriyl trioleate (CAS 122-32-7) evaluating the effects on the cell multiplication of Pseudomonas putida showed no adverse effects either after an exposure of 18 hours (EC50 > 0.8 mg/L). Based on all available information, it can be concluded that the Glyceride category members are not toxic to aquatic microorganisms.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.